A Phase 1/2 Study of AMG 193 in Combination with IDE397 in Subjects with Advanced MTAP-null Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Sep 2024 → 26 Mar 2026

Decision date (initial)

2024-07-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-504364-42-00

WHO UTN

U1111-1303-8733

ClinicalTrials.gov

NCT05975073

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others, Pharmacokinetic

Part 1: To study the maximum tolerated dose (MTD; the highest dose of the study drugs in combination which is safe to take and tolerated) or recommended dose of AMG 193 in combination with IDE397 in adult participants with locally advanced or metastatic MTAP-null solid tumors
Part 2: To study the anti-cancer activity of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non Small Cell Lung Cancer (NSCLC).

Secondary objectives 4

1. To describe the pharmacokinetics (PK) (how AMG 193 and IDE397 move in, around, and out of the body of the study participants) of AMG 193 when taken in combination with IDE397 in adult participants with locally advanced or metastatic MTAP-null solid tumors.
2. To study the anti-cancer activity of AMG 193 when taken in combination with IDE397 in adult participants with locally advanced or metastatic MTAP-null solid tumors
3. Part 2: To study the safety and tolerability of AMG 193 in combination with IDE397 in adult participants with locally advanced or metastatic MTAP-null NSCLC
4. To study the blood levels of symmetric dimethylation of arginine (SDMA is a waste product of cancer cells). Higher levels of SDMA can lead to loss in kidney function

Conditions and MedDRA coding

In Part 1, subjects with advanced MTAP-null solid tumors and, in Part 2, subjects with advanced MTAP-null Non Small-Cell Lung Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Evidence of homozygous loss of MTAP (null) and/or MTAP deletion
2. Presence of advanced/metastatic solid tumor not amenable to curative treatment. For Part 1, MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists. For Part 2, MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy.
3. Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product
4. Disease measurable as defined by RECIST v1.1
5. Adequate organ function as defined in the protocol
6. Archived tumor tissue. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before cycle 1 day 1 dosing.

Exclusion criteria 7

1. Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.
2. Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease
3. Cardiovascular and pulmonary exclusion criteria as defined in the protocol
4. Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis)
5. History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry.
6. Prior irradiation to > 25% of the bone marrow
7. Use of prescription medications that are known strong CYP3A4/5 inducers or strong CYP3A4/5 inhibitors within 7 days for CYP3A4/5 inhibitors, 14 days for CYP3A4/5 inducers or 5 half-lives, whichever is longer, prior to any dose of investigational medical product

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1: Dose-limiting toxicities, certain treatment related side effects that can occur in the first cycle of treatment. Adverse events (side effects) that occur after the start of treatment, or are related to treatment, or require significant intervention. Changes in vital signs (including blood pressure, heart rate, respiratory rate, and temperature), electrocardiograms, and clinical laboratory tests
2. Part 2: Whether the cancer responds to treatment, either a complete or a partial improvement of cancer lesions, as assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). RECIST is a scale set of rules used to determine if classify how a cancer patient is responding to treatment.

Secondary endpoints 4

1. Blood levels of AMG 193 and IDE397 when given in combination, including, but not limited to, maximal plasma concentration (Cmax) - that is the maximum amount of study drug present in the blood plasma, time to maximal plasma concentration (tmax) - that is the time required to achieve the maximum plasma concentration, and total drug levels over time.
2. The proportion of treated patients who respond to treatment by looking at tumor shrinkage or growth over time as assessed by CT or MRI imaging; the duration of time a tumor responds or does not increase in size while on study treatment; progression free survival (PFS) and overall survival (OS).
3. Part 2: Treatment emergent adverse events, serious adverse events, and changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests
4. Changes in blood levels of SDMA over time.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 15

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications